A photoactivatable molecule that can enter and kill malignant cancer and bacterial cells with high specificity has been tested.
Figure 1. Light-activated drug mimics typical metabolic molecules, behaving as "Trojan Horse" for easy entry and subsequent killing of malignant cells. Figure from: http://www.microbiologynutsandbolts.co.uk/uploads/7/8/9/4/7894682/trojan-horse_orig.jpg.
In the article titled, "Photoactivatable metabolic warheads enable
precise and safe ablation of target cells in vivo", published in Nature Communications, the authors describe a newly synthesized chemical platform that allows for non-toxic, visible-light activated and selective killing of early-onset and quickly progressing malignant cells.
The authors underwent rigorous synthetic derivatization of various photoactivatable functionalities, eventually discovering the benzoselenadiazole (SeNBD) group. This functionality exhibits significant photodynamic activity that allows for production of photosensitive metabolic warheads capable of targeting and killing bacterial infections (E. Coli) and aggressive cancers (Glioblastoma) consisting of high metabolic demand.
These molecules masquerade themselves alongside metabolic molecules like amino acids and saccharides, essentially behaving as an easily ingested “Trojan Horse” when combined with these typical foods molecules. This is aided by the greedy nature of bacterial and cancer cells, which consume higher concentrations of metabolites than typical healthy cells.
Figure 2. Photoactivatable metabolites masquerade as typical healthy metabolites.
Through this advantage, the drug can be delivered directly through the “front door” of the target malignant cells, by-passing typical defences, while remaining dormant until light activation. Once activated at the target site, as has been shown in both in vitro and in vivo studies, that the SeNBD molecules produce singlet oxygen capable of achieving precise malignant cell ablation without harming neighbouring healthy tissue, limiting potential side effects in vivo.
Figure 3. SeNBD metabolites gain swift entry to pathogenic cells in vivo, leading to malignant cell ablation through photoactivated singlet oxygen production.
This chemistry provides a promising new strategy for treatment of malignant cells, mediated by SeNBD molecules that act as one of the smallest non-toxic photoactivatable molecules to date. This strategy has the potential to open up new opportunities in interventional medicine, where precise killing of harmful cells with limited side-effects is a necessity.
Current work has focused on the use of both human cell and zebrafish models, which provides a strong platform for their efficacy. Further testing will be required on this technology to show if it is a safe method for treatment of early-stage cancers and drug-resistant bacteria in more in-vivo trials.
The findings of this research have been published in the Nature Communications Journal:
Benson, S., de Moliner, F., Fernandez, A. et al. Photoactivatable metabolic warheads enable precise and safe ablation of target cells in vivo. Nat. Commun. 12, 2369 (2021). https://doi.org/10.1038/s41467-021-22578-2.
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